Maternal Antibiotic Exposure Research Articles

Increased antibiotic resistance in preterm neonates under early antibiotic use.

A high burden of antibiotic resistance in preterm infants poses significant challenges to neonatal health. The presence of antibiotic resistance genes, along with alterations in signaling, energy production, and metabolic mechanisms, complicates treatment strategies for preterm infants, heightening the risk of ineffective therapy and exacerbating outcomes for these vulnerable neonates. Despite not receiving direct antibiotic treatment, preterm infants exhibit a concerning prevalence of antibiotic-resistant bacteria. This underscores the complex interplay of broader influences, including maternal antibiotic exposure during and beyond pregnancy and gestational complications like prolonged membrane ruptures. Urgent action, including cautious antibiotic practices and enhanced antenatal care, is imperative to protect neonatal health and counter the escalating threat of antimicrobial resistance in this vulnerable population.

Contributions of maternal prenatal infection and antibiotic exposure to offspring infection and risk for allergic respiratory conditions through age 5

ObjectivesTo determine if maternal prenatal infection increases risk of offspring postnatal infections through age 5 or diagnosis of respiratory allergy at age 5, independent of prenatal/postnatal antibiotic exposure. To evaluate if frequency of offspring infections mediates an association between prenatal infection and respiratory allergy at age 5. Study designSecondary data analyses were performed from the Child Health and Development Studies (CHDS), a prospective, longitudinal birth cohort that enrolled pregnant women from 1959 to 1966 (N = 19,044 live births). The sample included a subset of mother-offspring dyads (n = 2062) with abstracted medical record data from the prenatal period through age 5 that included information on antibiotic use, infection, and offspring respiratory allergy. ResultsSecond trimester maternal infection was associated with an increased risk of offspring infection (IRR = 1.23; 95% CI = 1.09–1.39; p = 0.001). No significant direct associations were detected between prenatal infection and diagnosis of offspring respiratory allergy. Offspring infection (OR = 1.17; 95% CI = 1.13–1.20; p < 0.001) and antibiotic exposure (OR = 1.28; 95% CI = 1.22–1.33; p < 0.001) were significantly associated with a diagnosis of offspring respiratory allergy. Respiratory allergy diagnosis risk was greater with increasing offspring infection exposure and antibiotics. There was a significant indirect effect of second trimester maternal infection on offspring respiratory allergy, due to infections and not antibiotic use, via offspring infection, indicating a partially mediated effect. ConclusionPrenatal maternal infection may contribute to increase risk for early childhood infections, which in turn, may increase risk for allergic conditions.

Association between maternal antibiotic exposure and emotional and behavioural problems in children at four years of age: A biomonitoring-based prospective study

BackgroundMaternal exposure to multiple antibiotics exposure during pregnancy has attracted extensive attention, but biomonitoring studies linking prenatal antibiotic exposure to emotional and behavioural problems in children are limited. MethodsA total of 2475 pregnant women from the Ma’anshan Birth Cohort were included, and the Strengths and Difficulties Questionnaire was completed when their children turned four years of age. The levels of 41 maternal urinary antibiotics and two metabolites were measured during the first, second and third trimesters. Generalized estimating equations and binary logistic regression models were applied to analyse the associations between maternal antibiotic exposure and emotional and behavioural problems in children and to determine the sensitive period, respectively. A quantile-based g-computation (QGC) approach was employed to examine the combined effects of multiple antibiotics on emotional and behavioural problems in children. ResultsOverall, florfenicol and preferred-as-veterinary antibiotic (PVA) exposure during pregnancy increased the risk of emotional problems in children, and ofloxacin exposure increased the risk of hyperactivity-inattention. Maternal exposure to trimethoprime, ciprofloxacin, florfenicol, other antibiotics and PVA exposure during the first trimester was positively associated with emotional problems in children. Second-trimester trimethoprime concentrations and third-trimester ciprofloxacin concentrations were positively associated with hyperactivity-inattention. Third-trimester veterinary antibiotic (VA) exposure was negatively associated with hyperactivity-inattention, and second-trimester VA and PVA exposure was negatively associated with peer problems. The QGC model revealed that mixed antibiotic exposure in the first trimester exacerbated the risk of childhood emotional problems (the contribution of ciprofloxacin is prominent), and mixed antibiotic exposure in the second trimester increased the risk of hyperactivity-inattention (the contribution of trimethoprime is prominent). ConclusionMaternal mixed antibiotic exposure during the first and second trimesters increases the risk of emotional problems and hyperactivity-inattention in children at four years of age.

Maternal-Fetal Exposure to Antibiotics: Levels, Mother-to-Child Transmission, and Potential Health Risks.

Due to its widespread applications in various fields, antibiotics are continuously released into the environment and ultimately enter the human body through diverse routes. Meanwhile, the unreasonable use of antibiotics can also lead to a series of adverse outcomes. Pregnant women and developing fetuses are more susceptible to the influence of external chemicals than adults. The evaluation of antibiotic exposure levels through questionnaire surveys or prescriptions in medical records and biomonitoring-based data shows that antibiotics are frequently prescribed and used by pregnant women around the world. Antibiotics may be transmitted from mothers to their offspring through different pathways, which then adversely affect the health of offspring. However, there has been no comprehensive review on antibiotic exposure and mother-to-child transmission in pregnant women so far. Herein, we summarized the exposure levels of antibiotics in pregnant women and fetuses, the exposure routes of antibiotics to pregnant women, and related influencing factors. In addition, we scrutinized the potential mechanisms and factors influencing the transfer of antibiotics from mother to fetus through placental transmission, and explored the adverse effects of maternal antibiotic exposure on fetal growth and development, neonatal gut microbiota, and subsequent childhood health. Given the widespread use of antibiotics and the health threats posed by their exposure, it is necessary to comprehensively track antibiotics in pregnant women and fetuses in the future, and more in-depth biological studies are needed to reveal and verify the mechanisms of mother-to-child transmission, which is crucial for accurately quantifying and evaluating fetal health status.

Intrapartum antibiotic use is associated with higher child body mass index (BMI) z-score at 4 years of age

Early life antibiotic exposure may increase obesity risk. We investigated if prenatal, intrapartum, or childhood antibiotic use is associated with child zBMI score at 4 yrs of age. We included data from the Alberta Pregnancy Outcomes and Nutrition (APrON) study, a prospective cohort study, on maternal and child antibiotic exposure and clinic measures of height and weight at age 4 (n = 408). Prenatal and childhood antibiotic exposure was not associated with zBMI score. Maternal intrapartum antibiotic exposure was associated with a zBMI score increase of 0.12 (95 % CI; 0.04, 0.46) in children at 4 years of age compared to non-exposure intrapartum.

Inappropriate prescribing contributes to high antibiotic exposure in young children in Australia.

Antibiotic exposure increases antimicrobial resistance and has also been associated with long-term harms, including allergies, inflammatory diseases and weight gain. We assessed antibiotic exposure in the first 2 years of life in Australian children, the factors influencing this and its appropriateness. Data from 1201 participants in the MIS BAIR randomized controlled trial were used. Multivariable logistic regression was used to identify factors associated with antibiotic exposure. At 1 and 2 years of age, exposure to at least one course of antibiotics was 43% and 67%, with the highest first antibiotic prescription rate between 9 and 18 months. Amoxicillin was the most frequently used antibiotic (59%), followed by cefalexin (7%). The most common diagnoses for which antibiotics were prescribed were respiratory tract infections from 0 to 6 months of age and otitis media from 6 to 12 months. Factors associated with antibiotic exposure from 0 to 12 months of age were delivery by Caesarean section (adjusted odd-ratio (aOR) 1.5, 95%CI 1.1-1.9), birth in winter (aOR 1.7, 95%CI 1.2-2.4), maternal antibiotic exposure during the last trimester of pregnancy (aOR 1.6, 95%CI 1.1-2.3), cessation of breastfeeding by 6 months of age (aOR 1.5, 95%CI 1.1-2.0) and day-care attendance (aOR 1.4, 95%CI 1.1-1.8). Based on parent-reported questionnaires, 27% of infants were treated in the first year of life for conditions unlikely to need antibiotic treatment. At least two-thirds of children were prescribed antibiotics in the first 2 years of life, and more than a quarter of these exposures may have been unnecessary.

Maternal Antibiotic Exposure and the Risk of Developing Antenatal Depressive Symptoms.

Background: Antenatal depression is common and has significant consequences. The literature suggests that antibiotic exposure may be associated with depression. Many individuals are exposed to antibiotics during pregnancy. Further investigation of the association between antenatal antibiotic use and the development of depression during pregnancy is needed. Methods: A national prospective observational cohort study of pregnant individuals was undertaken using an online survey, completed during the third trimester. Antenatal depressive symptoms (ADSs) were defined as having an Edinburgh Postnatal Depression Scale score of ≥13 and/or receiving a clinical diagnosis of depression. Results: One in six individuals (16.5%, n = 977) experienced ADSs during their pregnancy, of whom 37.9% received a depression diagnosis. There was no relationship between antibiotic use and the development of ADSs. Four factors were identified as significant independent predictors of ADSs: personal history of depression, severe nausea and vomiting causing an inability to eat, emotional abuse from an intimate partner within the prior 12 months, and not having a university degree. Conclusions: Antenatal antibiotic use was not associated with the development of ADSs. Given the high incidence of undiagnosed depression, new strategies and models of care that prioritise individuals with risk factors may be required to optimise antenatal care.

Oral Probiotic Supplementation in Pregnancy to Reduce Group B Streptococcus Colonisation (OPSiP trial): study protocol for a double-blind parallel group randomised placebo trial

IntroductionGroup B streptococcus (GBS), or Streptococcus agalactiae, remains a leading cause of neonatal morbidity and mortality. Canadian guidelines advise universal maternal screening for GBS colonisation in pregnancy in conjunction with...

Early prediction of pediatric asthma in the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort using machine learning

BackgroundEarly identification of children at risk of asthma can have significant clinical implications for effective intervention and treatment. This study aims to disentangle the relative timing and importance of early markers of asthma.MethodsUsing the CHILD Cohort Study, 132 variables measured in 1754 multi-ethnic children were included in the analysis for asthma prediction. Data up to 4 years of age was used in multiple machine learning models to predict physician-diagnosed asthma at age 5 years. Both predictive performance and variable importance was assessed in these models.ResultsEarly-life data (≤1 year) has limited predictive ability for physician-diagnosed asthma at age 5 years (area under the precision-recall curve (AUPRC) < 0.35). The earliest reliable prediction of asthma is achieved at age 3 years, (area under the receiver-operator curve (AUROC) > 0.90) and (AUPRC > 0.80). Maternal asthma, antibiotic exposure, and lower respiratory tract infections remained highly predictive throughout childhood. Wheezing status and atopy are the most important predictors of early childhood asthma from among the factors included in this study.ConclusionsChildhood asthma is predictable from non-biological measurements from the age of 3 years, primarily using parental asthma and patient history of wheezing, atopy, antibiotic exposure, and lower respiratory tract infections.ImpactMachine learning models can predict physician-diagnosed asthma in early childhood (AUROC > 0.90 and AUPRC > 0.80) using ≥3 years of non-biological and non-genetic information, whereas prediction with the same patient information available before 1 year of age is challenging.Wheezing, atopy, antibiotic exposure, lower respiratory tract infections, and the child’s mother having asthma were the strongest early markers of 5-year asthma diagnosis, suggesting an opportunity for earlier diagnosis and intervention and focused assessment of patients at risk for asthma, with an evolving risk stratification over time.

Maternal antibiotic exposure enhances ILC2 activation in neonates via downregulation of IFN1 signaling

Microbiota have an important function in shaping and priming neonatal immunity, although the cellular and molecular mechanisms underlying these effects remain obscure. Here we report that prenatal antibiotic exposure causes significant elevation of group 2 innate lymphoid cells (ILC2s) in neonatal lungs, in both cell numbers and functionality. Downregulation of type 1 interferon signaling in ILC2s due to diminished production of microbiota-derived butyrate represents the underlying mechanism. Mice lacking butyrate receptor GPR41 (Gpr41-/-) or type 1 interferon receptor IFNAR1 (Ifnar1-/-) recapitulate the phenotype of neonatal ILC2s upon maternal antibiotic exposure. Furthermore, prenatal antibiotic exposure induces epigenetic changes in ILC2s and has a long-lasting deteriorative effect on allergic airway inflammation in adult offspring. Prenatal supplementation of butyrate ameliorates airway inflammation in adult mice born to antibiotic-exposed dams. These observations demonstrate an essential role for the microbiota in the control of type 2 innate immunity at the neonatal stage, which suggests a therapeutic window for treating asthma in early life.

Maternal antibiotic exposure and childhood allergies: The Japan Environment and Children's Study.

The association of maternal antibiotic exposure during pregnancy with childhood allergic diseases remains unclear. We aimed to evaluate the association of maternal exposure to antibiotic use during pregnancy with childhood allergic diseases up to the age of 3 years by using data from a large Japanese birth cohort. We analyzed data on 78,678 pregnant women and their offspring aged 0 to 3 years. Prenatal antibiotic exposure was defined as the use of any antimicrobial agent during pregnancy. Information was collected from maternal interviews and medical record transcripts. The outcome variables in this study included preschool asthma, wheezing, food allergy, atopic dermatitis, eczema, allergic rhinoconjunctivitis, and any allergic disease. We used logistic regression analysis to evaluate the association of antibiotic exposure during pregnancy with childhood allergic diseases. Among the participating mothers, 28.5% used antibiotics during pregnancy. Antibiotic exposure during pregnancy was associated with preschool asthma (adjusted odds ratio [aOR]= 1.12 [95% CI= 1.06-1.19]), wheezing (aOR= 1.11 [95% CI= 1.07-1.15]), allergic rhinoconjunctivitis (aOR= 1.10 [95% CI= 1.03-1.17]) and any allergic disease (aOR= 1.09 [95% CI= 1.05-1.14]) in offspring up to age 3 years. In contrast, maternal antibiotic use was not associated with food allergies, atopic dermatitis, or eczema. Additionally, the significant associations were not influenced by the timing of antibiotic exposure, sex of the infants, or maternal history of allergies. Maternal antibiotic exposure during pregnancy is associated with an increased risk of childhood respiratory allergies.

Maternal Antibiotic Exposure and the Risk of Developing Antenatal or Postpartum Depressive Symptoms: The Maternal Experience Study Protocol.

Limited epidemiological evidence suggests a link between antibiotic use and developing depression. This study seeks to investigate this association in depth, using a cohort of pregnant individuals. The primary aim is to explore any association between the use of antibiotics during pregnancy and the development of antenatal depressive symptoms up to the third trimester, as well as the use of antibiotics during pregnancy and within 12 months postpartum and the development of postpartum depressive symptoms. A national prospective, observational, longitudinal cohort study has been designed to examine these relationships. A sample size of 1500 pregnant individuals has been sought for this study, assuming 10 potential predictor variables (including antibiotic use) in the final multiple logistic regression model and allowing for a 30% drop-out rate. The development of depressive symptoms is considered either a diagnosis by a medical doctor and/or a scoring 13 or higher on the Edinburgh Postnatal Depression Scale. Data will be collected during the third trimester and at 6 weeks, 6 months, and 12 months postpartum. These surveys include variables previously identified as associated with antenatal and postpartum depression (e.g., level of social support, experience of intimate partner abuse, and obstetric complications), as well as antibiotic and probiotic use. This study will provide an update on the prevalence of the symptoms of depression during pregnancy and postpartum and its associated risk factors. It will also, for the first time, comprehensively explore the potential association between antibiotic use during pregnancy and up to 12 months postpartum and the development of depressive symptoms.

Antibiotic use during pregnancy is linked to offspring gut microbial dysbiosis, barrier disruption, and altered immunity along the gut-lung axis.

Antibiotic use during pregnancy is associated with increased asthma risk in children. Since approximately 25% of women use antibiotics during pregnancy, it is important to identify the pathways involved in this phenomenon. We investigate how mother-to-offspring transfer of antibiotic-induced gut microbial dysbiosis influences immune system development along the gut-lung axis. Using a mouse model of maternal antibiotic exposure during pregnancy, we immunophenotyped offspring in early life and after asthma induction. In early life, prenatal-antibiotic exposed offspring exhibited gut microbial dysbiosis, intestinal inflammation (increased fecal lipocalin-2 and IgA), and dysregulated intestinal ILC3 subtypes. Intestinal barrier dysfunction in the offspring was indicated by a FITC-dextran intestinal permeability assay and circulating lipopolysaccharide. This was accompanied by increased T-helper (Th)17 cell percentages in the offspring's blood and lungs in both early life and after allergy induction. Lung tissue additionally showed increased percentages of RORγt T-regulatory (Treg) cells at both time points. Our investigation of the gut-lung axis identifies early-life gut dysbiosis, intestinal inflammation, and barrier dysfunction as a possible developmental programming event promoting increased expression of RORγt in blood and lung CD4+ T cells that may contribute to increased asthma risk.

Maternal antibiotic exposure increases total islet number and volume in the neonatal pancreas and reduces HbA1c and insulitis in adult female non‐obese diabetic mice

AbstractBackgroundEarly antibiotic treatment changes susceptibility to disease in rodent models for type 1 diabetes, but the impact that gestational antibiotics may have on pancreatic embryogenesis and β cell function later in life is still unknown.MethodsOur aim was to determine whether gestational antibiotics could change islet neogenesis and function in female non‐obese diabetic mouse offspring. Stereology of pancreatic islets and insulin measurements were therefore applied to 2‐week‐old pups from mothers either exposed or not to a broad‐spectrum cocktail of ampicillin (1 g/L), vancomycin (0.5 g/L) and neomycin (1 g/L) during pregnancy. The degree of insulitis, glycated haemoglobin (HbA1c), serum cytokines and endotoxin, fasting glucose and insulin, and glucose tolerance were tested in the prediabetic pups later in life. Inflammatory and glycaemic measurements were made on the breeding females, and the gut microbiota was analysed by 16S sequencing in both the mothers and pups.ResultsAntibiotics depleted the maternal microbiome and perturbed the normal gut colonisation trajectory in the pups. While Akkermansia and Rikenellaceae were later enriched in the treated pups, Bacteroides failed to colonise post‐treatment. Antibiotic treatment reduced blood glucose in the mothers, weight of the pups, and HbA1c and insulitis in the adult offspring and increased anti‐inflammatory CD4+ natural killer T cells. This was preceded by more than 50% increase in total islet number and volume, and increased insulin levels in postnatal life. No changes were observed in their homeostatic model assessment of insulin resistance (HOMA‐IR) and β cell function (HOMA‐β), serum endotoxin or cytokine levels later in life, but the glucose tolerance response was altered in the treated offspring, which suggested an improvement in β cell exhaustion that may have left the islets less vulnerable to destruction.ConclusionOur study highlights the importance of considering maternal microbiota‐modulating factors as determinants that may mitigate or aggravate diabetes via changes in islet maturation and β cell function in perinatal life.

Necrotizing enterocolitis: Bench to bedside approaches and advancing our understanding of disease pathogenesis.

Necrotizing enterocolitis (NEC) is a devastating, multifactorial disease mainly affecting the intestine of premature infants. Recent discoveries have significantly enhanced our understanding of risk factors, as well as, cellular and genetic mechanisms of this complex disease. Despite these advancements, no essential, single risk factor, nor the mechanism by which each risk factor affects NEC has been elucidated. Nonetheless, recent research indicates that maternal factors, antibiotic exposure, feeding, hypoxia, and altered gut microbiota pose a threat to the underdeveloped immunity of preterm infants. Here we review predisposing factors, status of unwarranted immune responses, and microbial pathogenesis in NEC based on currently available scientific evidence. We additionally discuss novel techniques and models used to study NEC and how this research translates from the bench to the bedside into potential treatment strategies.

Prenatal antibiotics exposure does not influence experimental allergic asthma in mice.

Changes in microbiome (dysbiosis) contribute to severity of allergic asthma. Preexisting epidemiological studies in humans correlate perinatal dysbiosis with increased long-term asthma severity. However, these studies cannot discriminate between prenatal and postnatal effects of dysbiosis and suffer from a high variability of dysbiotic causes ranging from antibiotic treatment, delivery by caesarian section to early-life breastfeeding practices. Given that maternal antibiotic exposure in mice increases the risk of newborn bacterial pneumonia in offspring, we hypothesized that prenatal maternal antibiotic-induced dysbiosis induces long-term immunological effects in the offspring that also increase long-term asthma severity. Therefore, dams were exposed to antibiotics (gentamycin, ampicillin, vancomycin) from embryonic day 15 until birth. Six weeks later, asthma was induced in the offspring by repeated applications of house dust mite extract. Airway function, cytokine production, pulmonary cell composition and distribution were assessed. Our study revealed that prenatally induced dysbiosis in mice led to an increase in pulmonary Th17+ non-conventional T cells with limited functional effect on airway resistance, pro-asthmatic Th2/Th17 cytokine production, pulmonary localization and cell-cell contacts. These data indicate that dysbiosis-related immune-modulation with long-term effects on asthma development occurs to a lesser extent prenatally and will allow to focus future studies on more decisive postnatal timeframes.

Association between maternal antibiotic exposure during pregnancy and childhood obesity in the Japan Environment and Children's Study.

The association between maternal antibiotic exposure during pregnancy and childhood obesity is still unclear. The study aimed to evaluate the association between prenatal exposure to antibiotics and obesity at age 3 years using data from a large Japanese birth cohort. The Japan Environment and Children's Study is a nationwide birth cohort study. In this study, singleton vaginal full-term births were included. Obesity was defined as body mass index ≥95th percentile according to child growth standards. Prenatal antibiotic exposure was defined as antimicrobial agent use during pregnancy and was collected from maternal interviews and medical record transcripts. Logistic regression analysis was performed to evaluate the association of prenatal antibiotic exposure with child obesity at 3 years. In the crude and adjusted models with all children, maternal antibiotic exposure during pregnancy showed a marginal relationship with child obesity at 3 years. In the analyses according to exposure period and sex, exposure to antibiotics during the second/third trimester was significantly associated with obesity at the age of 3 years in female infants, but not in male infants, although the exposure during the first trimester was not in both sexes. Maternal antibiotic exposure during mid/late pregnancy may result in child obesity.

Maternal antibiotics disrupt microbiome, behavior, and temperature regulation in unexposed infant mice.

Maternal antibiotic (ABx) exposure can significantly perturb the transfer of microbiota from mother to offspring, resulting in dysbiosis of potential relevance to neurodevelopmental disorders such as autism spectrum disorder (ASD). Studies in rodent models have found long-term neurobehavioral effects in offspring of ABx-treated dams, but ASD-relevant behavior during the early preweaning period has thus far been neglected. Here, we exposed C57BL/6J mouse dams to ABx (5mg/ml neomycin, 1.25μg/ml pimaricin, .075% v/v acetic acid) dissolved in drinking water from gestational day 12 through offspring postnatal day 14. A number of ASD-relevant behaviors were assayed in offspring, including ultrasonic vocalization (USV) production during maternal separation, group huddling in response to cold challenge, and olfactory-guided home orientation. In addition, we obtained measures of thermoregulatory competence in pups during and following behavioral testing. We found a number of behavioral differences in offspring of ABx-treated dams (e.g., modulation of USVs by pup weight, activity while huddling) and provide evidence that some of these behavioral effects can be related to thermoregulatory deficiencies, particularly at younger ages. Our results suggest not only that ABx can disrupt microbiomes, thermoregulation, and behavior, but that metabolic effects may confound the interpretation of behavioral differences observed after early-life ABx exposure.

Maternal stress and the maternal microbiome have sex-specific effects on offspring development and aggressive behavior in Siberian hamsters (Phodopus sungorus)

The gut microbiome, a community of commensal, symbiotic and pathogenic bacteria, fungi, and viruses, interacts with many physiological systems to affect behavior. Prenatal experiences, including exposure to maternal stress and different maternal microbiomes, are important sources of organismal variation that can affect offspring development. These physiological systems do not act in isolation and can have long-term effects on offspring development and behavior. Here we investigated the interactive effects of maternal stress and manipulations of the maternal microbiome on offspring development and social behavior using Siberian hamsters, Phodopus sungorus. We exposed pregnant females to either a social stressor, antibiotics, both the social stressor and antibiotics, or no treatment (i.e., control) over the duration of their pregnancy and quantified male and female offspring growth, gut microbiome composition and diversity, stress-induced cortisol concentrations, and social behavior. Maternal antibiotic exposure altered the gut microbial communities of male and female offspring. Maternal treatment also had sex-specific effects on aspects of offspring development and aggressive behavior. Female offspring produced by stressed mothers were more aggressive than other female offspring. Female, but not male, offspring produced by mothers exposed to the combined treatment displayed low levels of aggression, suggesting that alteration of the maternal microbiome attenuated the effects of prenatal stress in a sex-specific manner. Maternal treatment did not affect non-aggressive behavior in offspring. Collectively, our study offers insight into how maternal systems can interact to affect offspring in sex-specific ways and highlights the important role of the maternal microbiome in mediating offspring development and behavior.

Maternal anthropometric variables and clinical factors shape neonatal microbiome

Recent studies indicate the existence of a complex microbiome in the meconium of newborns that plays a key role in regulating many host health-related conditions. However, a high variability between studies has been observed so far. In the present study, the meconium microbiome composition and the predicted microbial metabolic pathways were analysed in a consecutive cohort of 96 full-term newborns. The effect of maternal epidemiological variables on meconium diversity was analysed using regression analysis and PERMANOVA. Meconium microbiome composition mainly included Proteobacteria (30.95%), Bacteroidetes (23.17%) and Firmicutes (17.13%), while for predicted metabolic pathways, the most abundant genes belonged to the class “metabolism”. We observed a significant effect of maternal Rh factor on Shannon and Inverse Simpson indexes (p = 0.045 and p = 0.049 respectively) and a significant effect of delivery mode and maternal antibiotic exposure on Jaccard and Bray–Curtis dissimilarities (p = 0.001 and 0.002 respectively), while gestational age was associated with observed richness and Shannon indexes (p = 0.018 and 0.037 respectively), and Jaccard and Bray–Curtis dissimilarities (p = 0.014 and 0.013 respectively). The association involving maternal Rh phenotype suggests a role for host genetics in shaping meconium microbiome prior to the exposition to the most well-known environmental variables, which will influence microbiome maturation in the newborn.